Guidelines on Diagnosis and Treatment of Malignant Lymphomas

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Classification system The World Health Organization (WHO) classification of neoplastic diseasesTumours of the haematopoietic and lymphoid tissues, 4th edition 2008 should be used. Diagnostic requirements for haematopathology diagnosis The diagnosis of lymphoma should be made, or reviewed, in a laboratory with the necessary specialist expertise and facilities. A pathology laboratory diagnosing lymphoma requires access to the following resources: a. Morphological expertise: Pathologists/haematologists involved in lymphoma diagnosis should have the necessary training to undertake this work. b. Immunophenotyping: All marker studies should be carried out using panels designed to test the validity of the morphological diagnosis and to demonstrate key prognostic variables. Marker studies should be carried out using flow cytometry and immunohistochemistry. An appropriate panel for the lymphoma sub-types is included in the lymphomaspecific sections in this document. c. Molecular techniques: The two main techniques are polymerase chain reaction (PCR) to detect monoclonality and some translocations, and fluorescence in situ hybridisation (FISH) techniques for translocations. These techniques should be used to confirm a provisional diagnosis and identify prognostic factors. Formal links with a molecular/cytogenetics service are required. d. Integrated reporting: Most patients with lymphoproliferative disorders have different specimens taken during their clinical course. Departments should have a mechanism for correlating results from lymph node biopsies, bone marrow aspirates and biopsies as well as different analyses of a single sample. Reporting A preliminary report should be available 5 working days after the specimen is received. This interim report should state specific outstanding investigations and be followed by a definitive report. Quality assurance and audit The main component of quality assurance is access to a robust and timely diagnostic process. An audit system designed to test the quality of the service should be in place. Laboratories should be able to provide users of the laboratory with details of their diagnostic criteria and technical methods. Laboratories should participate in the relevant quality assurance schemes for immunocytochemistry, flow cytometry and other diagnostic methods. Individual histopathologists should have access to a lymphoma review panel. Diagnosis – laboratory procedures and standards ■ Unfixed node biopsy imprint preparation – formalin preparation of material, snap freezing and disaggregation into single-cell suspension ■ WHO classification ■ Access to immunophenotyping, molecular techniques and molecular genetic techniques ■ Preliminary report within 5 working days ■ Systems of quality assurance in place: Standard Operating Procedures (SOPs); Lab Accreditation; National Quality Assurance Scheme ■ Access to review panel Multidisciplinary team (MDT) working MDT meetings are a desirable part of the diagnosis and management of lymphoma. The arrangements will vary with local circumstances but it is essential that diagnostic pathology and staging radiology be reviewed in both new and relapsed patients before making a management plan. This plan should be clearly documented in patients’ notes. 3
Standards in Staging of Lymphoma Ann Arbor staging classification for NHL The International Prognostic Index (IPI) Stage I IE II IIE III IIIE IIIS Area of involvement One lymph node region One extralymphatic (E) organ or site Two or more lymph node regions on the same side of the diaphragm One extralymphatic organ or site (localised) in addition to criteria for stage II Lymph node regions on both sides of the diaphragm One extralymphatic organ or site (localised) in addition to criteria for stage III Spleen (S) in addition to criteria for stage III The IPI is a prognostic model based on 5 parameters ■ Age (< 60 vs > 60 years) ■ ■ ■ Ann Arbor stage (I/II vs III/IV) Serum LDH (normal vs elevated) Extra-nodal involvement (≤ 1 site vs ≥ 1 site) ■ Performance status (0,1 vs 2–4) Based on these factors, patients with DLBCL can be divided into 4 prognostic categories as summarised below: Number of risk factors IIISE IV Spleen and one extralymphatic organ or site (localised) in addition to criteria for stage III One or more extralymphatic organs with or without associated lymph node involvement (diffuse or disseminated); involved organs should be designated by subscript letters (P, lung; H, liver; M, bone marrow) A = asymptomatic; B = symptomatic; unexplained fever of ≥ 38ºC; unexplained drenching night sweats; or loss of > 10% body weight within the previous 6 months). IPI risk group All patients Low-risk 0,1 Low/intermediate-risk 2 High/intermediate-risk 3 High risk 4, 5 The IPI describes a predictive model for patients with DLBCL at presentation. It has been adjusted for use in FL (FLIPI) and is less useful in ALCL, mediastinal B cell lymphoma and T-NHL. It should not used in Burkitt lymphoma or lymphoblastic lymphoma. 4
Page 1 and 2: Guidelines on Diag
Page 3 and 4: Guidelines on Diag
Page 5: Standards In Diagnosis of Lymphoma
Page 9 and 10: Pathologic Diagnosis of Lymphoma Ge
Page 11 and 12: Hodgkin lymphoma and its differenti
Page 13 and 14: Potential diagnostic pitfalls for l
Page 15 and 16: Summary of the usual Immunostaining
Page 17 and 18: Mature B-Cell Neoplasms Mature B-Ce
Page 19 and 20: Immunophenotype The tumour cells ex
Page 21 and 22: Lymphoplasmacytic Lymphoma Definiti
Page 23 and 24: Splenic Marginal Zone Lymphoma Defi
Page 25 and 26: Extra-nodal Marginal Zone B-Cell Ly
Page 27 and 28: Persistent / progressive disease or
Page 29 and 30: Follicular Lymphoma Definition and
Page 31 and 32: Potential Pitfalls a. Failure to di
Page 33 and 34: Mantle Cell Lymphoma Definition and
Page 35 and 36: Diffuse Large B-Cell Lymphoma Defin
Page 37 and 38: Stage 1 (bulky) and stages II - IV
Page 39 and 40: Treatment Standard chemotherapy for
Page 41 and 42: Burkitt Lymphoma/Leukaemia Definiti
Page 43 and 44: CODOX-M, (3 cycles) for low risk di
Page 45 and 46: Potential pitfalls Failure to diffe
Page 47 and 48: Precursor T Cell Neoplasms PRECURSO
Page 49 and 50: Mature T-Cell and NK-Cell Neoplasms
Page 51 and 52: Potential Pitfalls Treatment planni
Page 53 and 54: Recommended Investigations Evaluati
Page 55 and 56: Mycosis Fungoides and Sézary Syndr
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■ ■ Lymph node biopsy if there
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Primary Cutaneous CD30-Positive T-C
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Angioimmunoblastic T-Cell Lymphoma
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Prognostic factors The IPI is of li
Page 65 and 66:
Hodgkin Lymphoma (HL) Definition an
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Prognostic Factors / Index: i. Earl
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Immunodeficiency Associated Lymphop
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of cases and EBV in about 50%, but
Page 73 and 74:
Common Issues in Lymphoma Managemen
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Tumour Lysis Syndrome Tumour Lysis
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Haematopoietic Recombinant Growth F
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Follow-Up Follow-up for patients wi
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Follow-up for patients with concern
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77 Appendix
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Lower border: The lower of (i) 5 cm
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Glossary of Treatment Regimens Chlo
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2nd Edition. May 2010. Supported by
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Guidelines on Diagnosis and Treatment of Malignant Lymphomas

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